Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death
Abstract
Regulated glycosylation controls T cell processes, including activation, differentiation and homing by creating or masking ligands for endogenous lectins. Here we show that stimuli promoting T helper type 1 (TH1), TH2 or interleukin 17-producing T helper (TH-17) differentiation can differentially regulate the glycosylation pattern of T helper cells and modulate their susceptibility to galectin-1, a glycan-binding protein with anti-inflammatory activity. Although TH1- and TH-17-differentiated cells expressed the repertoire of cell surface glycans critical for galectin-1-induced cell death, TH2 cells were protected from galectin-1 through differential sialylation of cell surface glycoproteins. Consistent with those findings, galectin-1-deficient mice developed greater TH1 and TH-17 responses and enhanced susceptibility to autoimmune neuroinflammation. Our findings identify a molecular link among differential glycosylation of T helper cells, susceptibility to cell death and termination of the inflammatory response.
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Glycosylation state of some death receptors (e.g., FAS) impacts sensitivity of T lymphocytes to extrinsic apoptosis, influencing termination of inflammatory responses.
“Of note, the glycosylation state of some death receptors (e.g., FAS) has been shown to impact on the sensitivity of T lymphocytes to extrinsic apoptosis, hence influencing the termination of inflammatory responses [288–290].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [288]
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Regulation and Function of Proinflammatory TH17 Cells
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Galectin-3 Deficiency Reduces the Severity of Experimental Autoimmune Encephalomyelitis
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Dendritic Cell Metabolism and Function in Tumors
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Sweetening the hallmarks of cancer: Galectins as multifunctional mediators of tumor progression
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Self-citationCD44 Regulates Survival and Memory Development in Th1 Cells
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Schistosoma mansoni egg antigens induce Treg that participate in diabetes prevention in NOD mice
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Emerging Role of α2,6-Sialic Acid as a Negative Regulator of Galectin Binding and Function
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Self-citationA novel strategy for mammalian cell surface glycome profiling using lectin microarray
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Galectin-1 research in T cell immunity: Past, present and future
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Therapeutic potential of Galectin‐9 in human disease
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Glycans as Key Checkpoints of T Cell Activity and Function
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Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor–stroma crosstalk
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Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis
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Self-citationThe role of O-glycosylation in human disease
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N- and O-Glycans Modulate Galectin-1 Binding, CD45 Signaling, and T Cell Death
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Structural Features of Galectin-9 and Galectin-1 That Determine Distinct T Cell Death Pathways
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The HIV glycan shield as a target for broadly neutralizing antibodies
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Evolving Mechanistic Insights into Galectin Functions
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Translating the ‘Sugar Code’ into Immune and Vascular Signaling Programs
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Self-citationGalectin-7 in the Control of Epidermal Homeostasis after Injury
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Self-citation
- Authors
- Toscano, M. A., Bianco, G. A., Ilarregui, J. M., Croci, D. O., Correale, J., Hernandez, J. D., Zwirner, N. W., Poirier, F., Riley, E. M., Baum, L. G., & Rabinovich, G. A.
- Affiliations
- Universidad de Buenos Aires (AR)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- University of California, Los Angeles (US)
- London School of Hygiene & Tropical Medicine (GB)
- Corresponding author
- Rabinovich, Gabriel A
- ORCID
- Venue
- Nature Immunology
- Published
- 2007-06-24
- Volume
- 8
- Issue
- 8
- Pages
- 825-834
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2041659209
- Cited by
- 653
- References
- 52
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 22 · 2023: 22 · 2022: 46 · 2021: 31 · 2020: 35 · 2019: 20 · 2018: 36 · 2017: 25 · 2016: 33 · 2015: 36 · 2014: 37 · 2013: 34 · 2012: 40
- FWCI
- 18.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Immunology and Microbiology › Immunology › Galectins and Cancer Biology
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- galectin-1, T helper cell differentiation, Th1 cells, Th2 cells, Th17 cells, sialylation, cell death, cell surface glycans, lectin binding, autoimmune neuroinflammation
- MeSH terms
- Animals, Cell Differentiation, Encephalomyelitis, Autoimmune, Experimental, Flow Cytometry, Glycosylation, T-Lymphocytes, Helper-Inducer, Humans, Inflammation, Membrane Glycoproteins, Polysaccharides, Immunoblotting, T-Lymphocyte Subsets, Apoptosis, Th1 Cells, Th2 Cells, Adoptive Transfer, In Situ Nick-End Labeling, Interleukin-17, Galectin 1, Mice
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